김효인 (Harvard Medical School)

한빛사논문

조회377

Harvard Medical School

CV File 213 kb

Phytomedicine, Available online 30 July 2024 | https://doi.org/10.1016/j.phymed.2024.155926 The multi-herbal decoction SH003 alleviates LPS-induced acute lung injury by targeting inflammasome and extracellular traps in neutrophils

Hyo In Kim ^a,1, Yohan Han ^b,1, Mi-Hye Kim ^c,1, Mina Boo ^d, Kwang-Jin Cho^d, Hye-Lin Kim ^e, In-Seon Lee ^d,e, Ji Hoon Jung ^d,e, Woojin Kim ^d,e,f, Jae-Young Um ^d,e, Jinbong Park ^d,e,f, Seong-Gyu Ko ^d,e,f

^aBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

^bDepartment of Microbiology and Sarcopenia Total Solution Center, Wonkwang University School of Medicine, Iksan, Republic of Korea

^cCollege of Korean Medicine, Woosuk University, Jeonju, Republic of Korea

^dDepartment of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea

^eCollege of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea

^fKorean Medicine-Based Drug Repositioning Cancer Research Center, Kyung Hee University, Seoul, Republic of Korea

¹These authors contributed equally to this study and share first authorship.

Corresponding authors : Jinbong Park, Jinbong Park

Abstract

Background

Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, is known for its effects on cancer and immunoregulation.

Hypothesis/Purpose

Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo, and in vitro models.

Study Design and Methods

We performed in silico-based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation.

Results

Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003.

Conclusion

SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-08-12)
연구진국내(교신)+국외 연구진
분야 의약학 > 한의학

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